Significant under-representation of patients with chronic respiratory disease is done in multiple early reports of patients admitted to the hospital with COVID-19. This may be due to the widespread use of inhaled glucocorticoids among these patients. So a group of researchers tested whether inhaled glucocorticoids would prove to be an effective treatment for early COVID-19.

They performed an open-label, parallel-group, phase 2, randomized controlled trial of inhaled budesonide contrasting it with usual care. The study enrolled adults within 7 days of the onset of mild COVID-19 symptoms. 

In the trial, the participants were randomly assigned to inhaled budesonide or usual care stratified for age (≤40 years or >40 years), sex, and a number of comorbidities (≤1 and ≥2). Budesonide dry powder was delivered using a turbohaler at a dose of 400 μg per actuation, with two inhalations twice a day until symptom resolution. 

The primary endpoint was observing COVID-19-related urgent care visits, including emergency department assessment or hospitalization, which was analyzed for both the per-protocol and intention-to-treat (ITT) populations. The secondary outcomes were observing self-reported clinical recovery (symptom resolution), viral symptoms measured using the Common Cold Questionnaire (CCQ) and the InFLUenza Patient-Reported Outcome Questionnaire (FLUPro), body temperature, blood oxygen saturation, and SARS-CoV-2 viral load. 

The trial was stopped early after knowing that the study outcome would not change with further participant enrollment. Overall, 146 participants were enrolled for the study.They were randomly assigned equally (n=73) to usual care and to budesonide. 

For the per-protocol population -

• The primary outcome occurred in 14% of participants in the usual care group and 1% of participants in the budesonide group 

For the ITT population-

• The primary outcome occurred in 15% of participants in the usual care group and 3% participants in the budesonide group.
• The number needed to treat with inhaled budesonide to reduce COVID-19 worsening was found to be 8.
• The budesonide group showed 1 day shorter clinical recovery compared with the usual care group (median 7 days in the budesonide group vs 8 days in the usual care group).
• The mean proportion of days with a fever in the first 14 days was lower in the budesonide group than in the usual care group
• Lower proportion of participants with at least 1 day of fever was observed in the budesonide group comparing with the usual care group.
• As-needed antipyretic medication requirement was for fewer days in the budesonide group compared with the usual care group.
• Fewer participants in the budesonide group showed persistent symptoms at days 14 and 28 contrasting participants receiving usual care.
• The budesonide group showed significantly better mean total score change in the CCQ and FLUPro over 14 days compared with the usual care group.
• Blood oxygen saturation and SARS-CoV-2 load, measured by cycle threshold, were found to be similar in both groups.
• Only 7% of participants reported self-limiting adverse events in the Budesonide group, thus rendering it a safe treatment option.

It was thus concluded that early administration of inhaled budesonide reduces the likelihood of needing urgent medical care and also reduces the time to recovery after early COVID-19.

Ramakrishnan S, Nicolau DVJ, Langford B, Mahdi M, Jeffers H, Mwasuku C. et al. Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial, The Lancet Respiratory Medicine 2021 July; 9(7):763-72